Effective therapy was not available for treatment of acute stroke until 1995 when tissue plasminogen activator (tPA) was shown to improve neurologic and functional outcome in stroke patients who were treated within three hours of symptom onset. Currently, many patients do not qualify for tPA therapy because the present for evaluation beyond 3 hours after stroke onset. Attempts to expand the treatment window to 6 hours, using computerized tomography (CT) to select patients have been successful. Preliminary data suggest that new magnetic resonance imaging (MRI) techniques are likely to be more effective than CT for identifying patients who may respond favorably to tPA therapy. Investigators propose to apply robust new MRI techniques to investigate whether specific MRI profiles predict a favorable clinical response to intravenous tPA therapy administered between 3 and 6 hours after stroke onset. They hypothesize that patient subgroups who are likely to benefit from thrombolytic therapy can be identified based on a combination of blood flow parameters and an assessment of the degree of early ischemic brain injury - variables for which new MRI techniques, unlike CT, are extremely sensitive. In this multicenter, open-label, pilot clinical trial, 80 patients will receive an MRI scan with diffusion-weighted imaging, perfusion-weighted imaging and magnetic resonance angiography, immediately prior to receiving tPA therapy 3-6 hours after stroke onset. Two follow-up MRI scans will assess whether early reperfusion occurs and establish the final infarct volume. The clinical response to therapy will be determined both by the amount of improvement between the baseline NIH Stroke Scale (NIHSS) score and the 30-day score and the rate of achieving a "favorable clinical response" ((8 point improvement or complete recovery in the NIHSS score between baseline and 30 days) to tPA therapy. Three-month outcomes will be assessed with the Barthel Index and the Modified Rankin Scale. This study will provide important data needed to plan a randomized, placebo-controlled, clinical trial designed to determine whether stroke patients with specific MRI characteristics benefit from tPA therapy administered between 3-6 hours after stroke onset.